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September 4, 2026Frontiers in PharmacologyOpen Access

Drug spectrum and disproportionality signals for diabetes insipidus in FAERS: multi-method analysis, JADER cross-database assessment, and PubMed-based case-level evidence

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Why the study?

The study aimed to characterize reporting patterns and non-treatment drug safety signals for diabetes insipidus in FAERS, evaluate signal stability using disproportionality methods, and assess reproducibility in JADER.

Do non-treatment drugs increase the reporting of diabetes insipidus in pharmacovigilance databases?

Population

3,444 FAERS and 696 JADER diabetes insipidus reports

Comparison

Non-treatment primary suspect drugs vs non-events or other reports

Design

Pharmacovigilance disproportionality analysis across FAERS and JADER databases

Key result

Lithium demonstrated the strongest disproportionality signal for diabetes insipidus (ROR 483.85), with dexmedetomidine, sevoflurane, and hydrocortisone also showing significant associations.

Authors

YLYiqi LiYZYu ZhouJTJinghe Tian

Discussion

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Member takes

Overview

May warrant vigilance for diabetes insipidus with nervous system and antineoplastic agents; hypothesis-generating from disproportionality signals and requires prospective confirmation.

Study Design

Type

Observational (n=20,550,043)

Structured PICO

Do non-treatment drugs increase the reporting of diabetes insipidus in pharmacovigilance databases?

P
Population
20,550,043 deduplicated adverse event reports from the FAERS database, including 3,444 cases of diabetes insipidus, analyzed to identify non-treatment drug safety signals between 2004 and 2025.
E
Exposure
Non-treatment primary suspect drugs (excluding drugs used for DI diagnosis/treatment or AVP-deficiency states)
O
Outcome
Reporting of diabetes insipidus (defined by MedDRA Preferred Terms 'Diabetes insipidus' and 'Nephrogenic diabetes insipidus')safety

Main Result

Odds Ratio: 483.85 (95% CI 437.94–534.58)

Several non-treatment drugs, particularly nervous system, antineoplastic/immunomodulating, and systemic hormonal agents, showed persistent disproportionality signals for diabetes insipidus in FAERS, serving as hypothesis-generating signals.

Limitations

  • Disproportionality analyses based on spontaneous reports cannot establish causality or estimate incidence.
  • Interpretation is influenced by reporting behavior, drug utilization, and coding practices.
  • Central and nephrogenic DI are not always separable in public MedDRA Preferred Term-level data.
  • Available structured fields cannot fully distinguish baseline disease, clinical setting, and drug-induced events.
  • Disproportionality analyses based on spontaneous reports cannot establish causality or estimate incidence
  • Interpretation is influenced by reporting behavior, drug utilization, coding practices, and clinical context
  • Central and nephrogenic DI are not always separable in public MedDRA Preferred Term (PT)-level data
  • Published cases lacked exposed population denominators, comparator groups, or person-time

Cite This Study

Li et al. (2026) conducted an observational in Diabetes insipidus (n=20,550,043). Lithium and other non-treatment primary suspect drugs vs. All other reports in the database (non-cases) was evaluated on Disproportionality signal for diabetes insipidus (Reporting Odds Ratio) (ROR 483.85, 95% CI 437.94-534.58). Lithium demonstrated the strongest disproportionality signal for diabetes insipidus (ROR 483.85), with dexmedetomidine, sevoflurane, and hydrocortisone also showing significant associations.

synapsesocial.com/papers/6a9fdf8e29d9e05a3f618b82https://doi.org/10.3389/fphar.2026.1840741
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